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The pharmacodynamic and clinical trial evidence for statin dose
Author(s) -
Dimmitt Simon B.,
Stampfer Hans G.,
Warren John B.
Publication year - 2018
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.13539
Subject(s) - atorvastatin , medicine , statin , ed50 , randomized controlled trial , myocardial infarction , pharmacodynamics , pharmacology , adverse effect , cardiology , pharmacokinetics , receptor
Statin doses around estimated effective dose 50 (ED50) can reduce myocardial infarction by over 25% and mortality by around 10%. Being a competitive enzyme inhibitor, statin efficacy plateaus at doses that are multiples above the ED50, whilst on‐ and off‐target adverse events increase in number and severity with increasing dose. For example, myopathy has been shown to increase by up to 29‐fold and liver dysfunction by up to nine‐fold as statin dose is increased. Doses of up to 40‐fold ED50 have been promoted, but above five‐fold ED50, for example 10 mg of atorvastatin, there is no randomized controlled clinical trial evidence that coronary mortality is lowered, or that survival is increased.